CD44 is a transmembrane glycoprotein which functions as cell surface hyaluronic acid (HA) receptor (Aruffo A et al. Cell. 1990 Jun. 29; 61(7):1303-13.). CD44 is involved in cell adhesion on HA, cell migration and HA metabolism.
We have discovered earlier that soluble recombinant CD44 hyaluronic acid binding-domain (CD44-HABD) inhibits angiogenesis in vivo (Päll T et al, Oncogene. 2004 Oct. 14; 23(47):7874-81.). Importantly, CD44-HABD inhibits angiogenesis and endothelial cell proliferation independently of HA-binding (Päll et al, supra). Therefore the inventors hypothesized that CD44 binds to another ligands besides HA on endothelial cells to exert its effects.
Thus, there is a need to find molecules interacting with CD44-HABD, in order to further understanding and control angiogenesis and endothelial cell proliferation, and to provide therapeutic treatment for related states. It is therefore an object of the invention to identify such molecules.
Vimentin is known to be overexpressed in tumor endothelium and targeting vimentin using an antibody has been shown to inhibit angiogenesis both in vivo and in vitro (WO/2007/039255).